Cytogenetic Features in Myelodysplastic Syndromes

BELLI, CAROLINA; BESTACH, YESICA; CORREA, WALTER A; SAKMANN, FEDERICO ; ENRICO, ALICIA; LARRIPA, IRENE

Myelodysplastic Syndromes: From pathogenesis to Diagnosis and Therapy

Biomedical Books, Nova Science Publishers

Lugar: New York; Año: 2013; p. 61 - 82

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases characterized by refractory cytopenia(s) as a result of ineffective hematopoiesis, in the context of a mostly normo/hypercellular bone marrow (BM), with variable risk of progression to acute myeloid leukemia (AML). Similar to most malignancies, MDS likely arise from a genetically transformed primitive hematopoietic stem cell, while subsequent genetic and epigenetic changes contribute to their development and progression. Immune, cytokine and stromal responses in the host are important to define the disease phenotype. Approximately 50% of patients show abnormal karyotype not associated with any particular chromosomal alteration. They are most often characterized by total or partial loss of material from chromosomes 5, 7, 13, 17, 20 or a sex chromosome, as well as a relatively high incidence of genetic gains such as trisomy 8, 19 and 21, while recurrent translocations or other structural abnormalities are less common. The great variability in the natural history of MDS complicates decision-making regarding therapies, and the inclusion of cytogenetic findings into different prognostic systems has contributed to improvement in prognostic assessment. Karyotype has been recognized as an independent prognostic factor in MDS since 1993 when the Lille system confirmed that the presence of complex karyotype was associated with a poor prognosis. In 1997, the International prognostic scoring system (IPSS) recognized three cytogenetic risk groups where some particular alterations (-Y, 5q-, -7/7q-, +8 and 20q-) were associated with a specific prognosis, thus cytogenetics becoming a widely accepted tool to assess prognosis. However, the IPSS included in the intermediate group a number of low frequency cytogenetic alterations that make it heterogeneous and is still a matter of debate. Later on, the IPSS was revised and the risk of some less frequent cytogenetic abnormalities (i.e. rearr3q, 11q-, 12p-, i17q, +19 and +21) was specified, splitting cytogenetics into five categories (IPSS-R). Recently, we have developed an alternative but complementary strategy to the original IPSS, where isolated deletions, excluding 7q-, were placed into good prognostic findings and monosomal karyotypes (MK) among the worse ones (IPSS-MK). New published data have confirmed the unfavorable prognosis associated with MK in, not only AML, but also MDS. This chapter thus focuses on the cytogenetic profile of MDS describing clinical, molecular background and prognostic relevance of chromosome findings. We also review different cytogenetic risk stratifications that have been published during the past twenty years since the karyotype was first recognized as an independent factor for predicting prognosis in MDS.